Acrylonitrile which is extensively used for the synthesis of acrylic fibers and plastics, is a potent acute toxin, a mutagen, a teratogen and a carcinogen. Yet little is known about the in vivo biologic actions of this reactive electrophile apart from the fact that it is capable of depleting the antioxidant glutathione in multiple organs and that a minor proportion of the administered dose is converted to cyanide which is excreted as thiocyanate. Our objective is to elucidate the biologic fate of acrylonitrile, particularly to determine if this reactive electrophile covalently binds to tissue nucleophiles by cyanoethylation in vivo as it does in vitro. Radiolabelled 14(C-2,3)-acrylonitrile will be used to monitor the uptake, tissue distribution and excretion of this compound as well as its proposed covalent binding to macromolecules and formation of glutathione conjugates. Sites and possible enzymic mechanisms of glutathione conjugation and cyanide liberation will be characterized. Effects of treatments which modulate acute acrylonitrile toxicity (cysteine, fasting and phenobarbital) on its potentially injurious biologic reactions, i.e., cyanoethylation and cyanide liberation, will be examined. These studies will provide a clearer understanding of the relationships between acrylonitrile toxicity and biotransformation, begin to define the molecular events responsible, and guide future studies of the chemical mechanisms underlying the toxicity of structurally related aliphatic nitriles.